Vascular alterations in aging normotensive and hypertensive strains of rats
Description
After a saline flush containing 1 ml of 1% NaNO(,2), a vasodilator, 42 female normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) from 3 to 24 months of age were sacrificed by an intracardiac perfusion of 3% glutaraldehyde in 0.1M phosphate buffer, pH 7.3. Proximal portions of the left coronary arteries, jejunal branches of the superior mesenteric arteries which gave rise to the terminal mesenteric arcades, and 3-5 mm thick cross-sectional slices of the jejunum were isolated, postfixed in 1% OsO(,4) for 1 hr, dehydrated in ethanols and embedded in Epon 812. Mean systolic blood pressure was always significantly different between WKY and SHR; it increased steadily with age in SHR (144 to 209 mm Hg) and decreased steadily in WKY (121 to 89 mm Hg). Mean relative ventricular weight was always higher in SHR compared to WKY and increased with age (0.46 to 0.74% body weight in SHR and 0.40 to 0.41% body weight in WKY). Significant differences in this parameter were observed at 1 and 2 years of age between WKY and SHR. Mean medial thickness/lumen diameter ratio (measured with a calibrated ocular micrometer) in jejunal arterioles was always significantly higher in SHR compared to WKY (p < 0.0005). This ratio showed no significant changes with age in WKY, but in SHR it increased significantly from 3 months to 1 year and then decreased significantly from 1 year to 2 years. The ratio increase in SHR was associated with a significant increase in medial thickness; the ratio decrease was associated with a significant increase in lumen diameter In the coronary arteries, lipofuscin-like inclusions in smooth muscle cells (SMC) developed with age. Compared to WKY, organelles were increased in SHR endothelial cells, SMC and fibroblasts at all ages. Compared to WKY and increasing with age, the following alterations were observed in SHR. Endothelial Weibel-Palade bodies increased and SMC processes extended into the subendothelial space. Orcein stain suggested active synthesis of elastin by SMC. SMC developed membranous whorls (as did fibroblasts in the adventitia), cell invaginations, cell processes and nuclear lobulation. SMC degenerative alterations included loss of myofilaments, focal cytoplasmic necrosis, necrotic cells with pyknotic nuclei, and formation of cell debris. Collagen, basement membrane-like material (determined with silver methenamine) and debris accumulated in the extracellular space. Fibroblast-like cells were noted in the media. Medial degenerative alterations were most prominent at the medio-adventitial junction in the younger animals and progressed toward the intima with increasing age in SHR. A non-elastic homogeneous substance with intimate relation to debris was noted in the adventitia of aged SHR Similar ultrastructural alterations were noted in SHR mesenteric arteries, although the changes were, in general, not as extensive as in coronary arteries. Fine structural degenerative alterations were not observed in SHR jejunal arterioles These observations indicate that structural alterations in the cardiovascular system of SHR progress with increasing age and that significant differences (qualitative and quantitative) in various parameters of vascular structure are observed between WKY and SHR, even in advanced age